Psychostimulants and cognition: a continuum of behavioral and cognitive activation

Abstract

Psychostimulants such as cocaine have been used as performance enhancers throughout recorded history. Although psychostimulants are commonly prescribed to improve attention and cognition, a great deal of literature has described their ability to induce cognitive deficits, as well as addiction. How can a single drug class be known to produce both cognitive enhancement and impairment? Properties of the particular stimulant drug itself and individual differences between users have both been suggested to dictate the outcome of stimulant use. A more parsimonious alternative, which we endorse, is that dose is the critical determining factor in cognitive effects of stimulant drugs. Herein, we review several popular stimulants (cocaine, amphetamine, methylphenidate, modafinil, and caffeine), outlining their history of use, mechanism of action, and use and abuse today. One common graphic depiction of the cognitive effects of psychostimulants is an inverted U-shaped dose-effect curve. Moderate arousal is beneficial to cognition, whereas too much activation leads to cognitive impairment. In parallel to this schematic, we propose a continuum of psychostimulant activation that covers the transition from one drug effect to another as stimulant intake is increased. Low doses of stimulants effect increased arousal, attention, and cognitive enhancement; moderate doses can lead to feelings of euphoria and power, as well as addiction and cognitive impairment; and very high doses lead to psychosis and circulatory collapse. This continuum helps account for the seemingly disparate effects of stimulant drugs, with the same drug being associated with cognitive enhancement and impairment.

Fig. 1.

Donald Hebb’s “optimal arousal theory,” as depicted in Fig. 2 in Hebb (1955). Redrawn from content in the public domain. Hebb was describing Schlosberg’s “level of activation continuum.” This theory is often conflated, somewhat incorrectly, with the Yerkes-Dodson law.

Fig. 2.

Behavioral activation continuum as described by Lyon and Robbins (1975). Redrawn from their Fig. 3, with permission. The relative distribution and availability within a given time sample of varying activities in the rat is determined by the increasing dose-response effect of d-amphetamine.

Fig. 3.

One of the early labels for Coca-Cola. Note its emphasis on performance-enhancing effects and its description as a psychiatric panacea (Ludlow Santo Domingo Library). The actual amount of coca leaves per glass was described by Coca-Cola in an editorial letter as 0.11 g (Candler, 1891), or enough to produce about 0.5 mg of cocaine, less than 0.01 mg/kg in an adult (Jenkins et al., 1995).

Fig. 4.

Fear memory was enhanced at low doses and impaired at high doses of d-amphetamine (A), cocaine (B), or modafinil (C) in mice. Data redrawn with permission from Wood and Anagnostaras (2009), Wood et al. (2007), and Shuman et al. (2009), respectively.

Fig. 5.

Prevention of sleep deprivation–related performance decline in flight performance by repeated doses of 10 mg of amphetamine (Dexedrine). Data are from the U.S. Army Aeromedical Research Laboratory. Redrawn with permission from Fig. 7 in Caldwell (2003).

Fig. 6.

Cognitive enhancement of IQ by 20 mg of amphetamine (Benzedrine). An early formal study of amphetamine’s cognitive-enhancing effects by Sargant and Blackburn (1936). Twenty milligrams of amphetamine improved IQ in mentally ill patients by almost a full standard deviation. Scores here (drawn from their Table 1) have been adjusted to a scale of 100, and the Benzedrine group includes subjects tested 90 or 150 minutes after administration (both groups performed similarly). Drawn from Sargant and Blackburn (1936) with permission from Elsevier.

Fig. 7.

d-Amphetamine reduces motor activity and increases memory in both ADHD and healthy boys. (A) Reduction of motor activity in normal and ADHD boys after 0.5 mg/kg d-amphetamine sulfate. (B) Improvement in verbal memory in normal and ADHD boys after d-amphetamine administration. Data are drawn with permission from Table 4 (activity) and Table 9 (memory) in Rapoport et al. (1980). Data shown are the mean ± 1 S.E.

Fig. 8.

Methylphenidate is effective in treating ADHD symptoms. (A) Reduction in ADHD symptomatology with methylphenidate (Concerta, 18 mg, roughly 0.5 mg/kg) treatment. (B) Improvement in WCST cognitive scores with Concerta treatment. Drawn from data reported in Tables 1 and 2 from Yildiz et al. (2011). Data shown are the mean ± 1 S.E.

Fig. 9.

Cognitive-enhancing properties of caffeine. It is not unusual for caffeinated products (and those containing guarana, which contains considerable caffeine) to claim cognitive enhancement. “Think” gum produced memory enhancement in word list learning (Davidson, 2011; adapted from their Fig. 2B). Davidson is also the founder of the company, raising some caution about the impressive results. Redrawn from Davidson (2011) with permission from Elsevier.

Fig. 10.

Continuum of psychostimulant activation. Increasing cognitive activation as stimulant dose increases initially produces increased wakefulness and cognitive enhancement. These are the desired therapeutic effects. As dose increases, a sense of power and euphoria can ensue; these are the effects addicts seek and are accompanied by cognitive deficits. Higher doses can result in overdose, psychosis, coma, and eventual circulatory collapse.